Therapeutics GI Ronald Flashcard

Functions of the Liver

Hepatocytes perform liver’s metabolic functions

  • Formation and excretion of bile
  • Regulation of carbohydrate homeostasis
  • Lipid synthesis and secretion of plasma lipoproteins
  • Control of cholesterol metabolism
  • Formation of serum albumin, clotting factors, enzymes, urea, and numerous other proteins
  • Metabolism and detoxification of medications and other foreign substances
  • Stores glycogen, iron, vitamins, and minerals

Functions of the Pancreas

  1. Secretes fluid-containing digestive enzymes into the duodenum
  2. Secretes the hormones insulin and glucagon, which help regulate sugar levels in the bloodstream
  3. Secretes into the duodenum large of quantities of Na+HCO3 needed to neutralize the acid coming from the stomach

Functions of the Gallbladder
Primary function is to store and release bile
Functions of Bile

Bile = bile salts, bilirubin, phospholipids, cholesterol, bicarbonate, and water

Emulsifies fat and fat-dependent vitamins (A,D,E,K) to promote absorption

Disorders of the Gallbladder

  1. Cholelithiasis = gallstones
  2. Cholecystitis = inflammation of the gallbladder
  3. Cholestasis = back up of bile in the liver

General Symptoms of Liver Abnormalities

  • Fatigue, weakness
  • Nausea, poor appetite, weight loss
  • Steatorrhea — loose, fatty stool

Skin Manifestations of Liver Abnormalities

  • Spider angiomas
  • Palmar erythema
  • Pruritis
  • Clubbing

Cardiovascular Findings/Blood Abnormalities of Liver Abnormalities

  • Tachycardia
  • Hypotension
  • Anemia
  • Leukopenia
  • Thrombocytopenia
  • Coagulopathy

Lab Tests for Pancreatic Injury

Amylase (N = 40-140 U/L)

  • Released into blood when the pancreas is diseased, injured, or inflamed
  • Non-specific alone — used in combination with signs/symptoms

Lipase (N = 0-160 U/L)

  • Released into the blood when the pancreas is diseased, injured, or inflamed
  • Non-specific alone — used in combination with signs/symptoms

 

 

 

 

Lab Tests for Liver Injury: Aminotransferases


  • Aspartate transaminase (AST) = 5-43 IU/L
  • Alanine transaminase (ALT) = 8-40 IU/L
  • Enzymes located in the cytoplasm of hepatocytes
  • Elevated with hepatocellular injury

High Levels (> 20x) = acute viral, drug-induced or ischemic

 

EtOH liver dz = rarely ALT > 500 IU/L

 

Moderate elevation (100-300 IU/L) = chronic liver dz

 

Ratio of AST:ALT > 2 = suggests alcoholic liver dz

 

AST can be elevated in rhabdomyolysis, heart damage, or brain tissue damage

    Lab Tests for Liver Injury: Lactate Dehydrogenase

    • N = 85-285 IU/L
    • Enzyme found in almost all body tissues and released when cells are damaged or destroyed
    • Insensitive for hepatocellular injury — but sensitive for cancers involving the liver
    • Also indicates hemolysis, MI, or PE

    Lab Tests for Cholestasis

    Bilirubin

    • Total bilirubin (N = < 1.2 mg/dL)
    • Direct bilirubin (N = < 0.3 mg/dL)

    Alkaline Phosphatase

    • N = 30-115 IU/L
    • cellular enzyme with high concentrations in the liver and bone
    • Found in cells that join to form the bile ducts
    • Elevated when bile flow through the bile duct is disrupted

    Gamma-Glutamyl Transpeptidase

    • N = < 50 IU/L
    • Liver enzyme that is very sensitive to changes in liver function
    • Levels of GGT correlate well with ALP
    • Combination is sensitive and specific for biliary tract disease

     

    Etiologies for Hyperbilirubinemia

    Unconjugated Bilirubin

    • Excessive production = hemolysis
    • Immature enzyme system = Jaundice of newborn/ prematurity
    • Inherited defects = Gilbert syndrome, Crigler-Najjar syndrome

    Conjugated Bilirubin

    Impaired Intrahepatic Excretion

    • hepatocellular disease = hepatitis, cirrhosis, medications
    • intrahepatic cholestasis = pregnancy, medications
    • congenital = Dubin-Johnson syndrome, Rotor syndrome

    Obstruction

    • extrahepatic = calculus, stricture, neoplasm
    • intrahepatic = sclerosing cholangitis, cirrhosis, neoplasm

    Test for Hepatic Synthetic Capacity

    PT/INR

    • N = < 1
    • Liver’s ability to synthesize Vit-K depedent clotting factors (II, V, VII, X)
    • Elevations indicate severe hepatocellular dysfunction and indicate progression to advanced cirrhosis

    Serum Albumin

    • N = 3.9-5
    • Most abundant protein in the blood plasma
    • Maintains oncotic pressure, nourishes tissues, and transports hormones, vitamins, drugs, and ions like Ca2+ throughout the body
    • Synthesized in the liver and is extremely sensitive to liver damage
    • Decreased levels with kidney disease, malnutrition, alcoholism, inflammation, and shock

    Child-Pugh Classification

    • Quantifies effects of cirrhotic process
    • Based on combination of clinical and laboratory data
    • Used for drug-dosing adjustments
    • Limitations = relies on subjective scoring for ascites and encephalopathy

    Grade A (mild) = < 7 pts

    Grade B (moderate) = 7-9 pts

    Grade C (severe) = 10-15 pts

    Mayo End-Stage Liver Disease (MELD)

    • The accepted classification system used by the United Network of Organ Sharing (UNOS)
    • Used in the allocation of livers for transplant
    • Relies solely on objective data
    • Not currently used for medication dosing
    • Score range from 6 (less ill) to 40 (gravely ill)

    4 MELD Levels for organ allocation

    > 25
    24-19
    18-11
    < 10

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